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We administered two cholecystokinin antagonists to dogs intravenously (i.v.) and into the third cerebral ventricle (i.t.v.). Proglumide (3-300mg/kg/hr i.v. or 0.1-10mg/dog i.t.v.) reversed the satiety previously shown by mongrel dogs after i.t.v. CCK-8. A new glutaramic derivative, CR1409, blocked this satiety even more strongly when administered by either route. Proglumide increased proglumide levels in ventricular fluid, indicating its ability to cross the blood-brain barrier. However, i.t.v. proglumide did not appear in the blood during the observation period. These results suggest that systemic proglumide and CR1409 act as antagonists of the central CCK receptor concerning satiety in dogs; intravenously administered proglumide was found to cross the blood-brain barrier and partially but significantly reverse the satiety caused by CCK-8.

The Effect of Cholecystokinin Antagonists on Satiety induced by Cholecystokinin Octapeptide in Dogs